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Combination benefit of a pyrimidylpiperazine derivative (Y-40138) and methotrexate in arthritic rats

Combination benefit of a pyrimidylpiperazine derivative (Y-40138) and methotrexate in arthritic rats

European Journal of Pharmacology 497(3): 351-359

Anti-tumor necrosis factor-alpha (TNFalpha) antibody in combination with methotrexate dramatically decreases joint destruction in rheumatoid arthritis. The aim of this study was to examine combined treatment with N-(1-(4- ((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)phenyl)cyclopropyl) acetamide HCl (Y-40138) and methotrexate in rat adjuvant-induced arthritis. The increase in hindpaw volume and joint destruction was suppressed by single therapeutic administration (days 15-20) of Y-40138 (30 mg/kg, p.o.), but not by prophylactic administration (days 1-9). However, arthritic progression was suppressed by single prophylactic administration of methotrexate (0.3 mg/kg, p.o.), but not by therapeutic administration. Combined administration (days 10-20) of Y-40138 (0.3-1 mg/kg) and methotrexate (0.03 mg/kg) synergistically suppressed the increase in hindpaw volume and joint destruction. We concluded that Y-40138 in combination with methotrexate synergistically suppressed arthritic progression. These data suggest that combined treatment with Y-40138 and methotrexate may increase efficacy of therapy for rheumatoid arthritis. Copyright 2004 Elsevier B.V. All rights reserved.

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Accession: 011874205

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PMID: 15336954

DOI: 10.1016/j.ejphar.2004.07.058

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